Covalent Template-Directed Synthesis

Oligomeric molecules composed of defined sequences of different building blocks represent a huge area of as yet unexplored chemical space. The nanotechnology that constitutes the natural world is built almost entirely from such molecules, i.e. proteins and nucleic acids. Nature teaches us that sequence polymers are likely to provide access to a wide range of functionality that is not accessible with small molecules or conventional synthetic polymers. The problem with synthetic sequence polymers is that we do not have useful tools to make them. Biology uses nucleic acid templates both for synthesis of long chains of defined sequence, and for evolutionary searching of sequence space to find which sequences have interesting properties. Thus the development of efficient template synthesis protocols would open the way to exploitation of synthetic sequence polymers. An abiological version of the in vitro selection experiment would allow exploration of sequence space to identify new functional synthetic polymers. The aim of this project is to develop a powerful new chemical approach for reliable template synthesis. Biology uses hydrogen-bonds to bind monomers to a template, and in principle, the same strategy could by applied to synthetic sequence polymers. However, there are major limitations in using non-covalent chemistry for such templating processes. If we are to find a reliable chemical method for template synthesis, a different approach will be required. This project will explore an alternative to non-covalent templating, covalent templating using labile covalent chemistry.